rs139983860

Variant names:

• chr6-31954568-CTCTCGG-C
• rs139983860
• NM_002904.6:c.723_728delCCGAGA

Your query was ambiguous. Multiple possible variants found:

• chr6-31954568-CTCTCGG-C
• chr6-31954568-CTCTCGG-CTCTCGGTCTCGG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_002904.6(NELFE):​c.723_728delCCGAGA​(p.Asp241_Arg242del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00475 in 1,607,668 control chromosomes in the GnomAD database, including 284 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (135 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (149 hom.)
• Consequence: NELFE NM_002904.6 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

Genes affected

NELFE (HGNC:13974): (negative elongation factor complex member E) The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002904.6
• BP6: Variant 6-31954568-CTCTCGG-C is Benign according to our data. Variant chr6-31954568-CTCTCGG-C is described in ClinVar as Benign. ClinVar VariationId is 784497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002904.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	NM_002904.6	MANE Select	c.723_728delCCGAGA	p.Asp241_Arg242del	disruptive_inframe_deletion	Exon 7 of 11	NP_002895.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	ENST00000375429.8	TSL:1 MANE Select	c.723_728delCCGAGA	p.Asp241_Arg242del	disruptive_inframe_deletion	Exon 7 of 11	ENSP00000364578.3	P18615-1
	NELFE	ENST00000375425.9	TSL:2	c.744_749delCCGAGA	p.Asp248_Arg249del	disruptive_inframe_deletion	Exon 7 of 11	ENSP00000364574.5	P18615-3
	NELFE	ENST00000948308.1		c.741_746delCCGAGA	p.Asp247_Arg248del	disruptive_inframe_deletion	Exon 8 of 12	ENSP00000618367.1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3745 AN: 152138 Hom.: 136 Cov.: 31

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00687 AC: 1691 AN: 246010 AF XY: 0.00516

Gnomad AFR exome AF: 0.0864

Gnomad AMR exome AF: 0.00605

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00268 AC: 3894 AN: 1455412 Hom.: 149 AF XY: 0.00233 AC XY: 1688 AN XY: 723284

African (AFR) AF: 0.0860 AC: 2875 AN: 33440

American (AMR) AF: 0.00668 AC: 297 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25508

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000647 AC: 55 AN: 84986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00680 AC: 39 AN: 5732

European-Non Finnish (NFE) AF: 0.000187 AC: 207 AN: 1108332

Other (OTH) AF: 0.00700 AC: 421 AN: 60124

GnomAD4 genome AF: 0.0246 AC: 3749 AN: 152256 Hom.: 135 Cov.: 31 AF XY: 0.0238 AC XY: 1774 AN XY: 74438

African (AFR) AF: 0.0844 AC: 3505 AN: 41510

American (AMR) AF: 0.0106 AC: 162 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68028

Other (OTH) AF: 0.0236 AC: 50 AN: 2116

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.0288

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=106/94	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs139983860; hg19: chr6-31922345;